Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort

Rebecca A Kaye,Karina Patasova,Andrew J Lotery,Praveen J Patel,Pirro Hysi

doi:10.1038/s41598-021-02631-2

Abstract

To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10–67). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.

Highlights

To evaluate the influence Age-related macular degeneration (AMD) risk genomic variants have on macular thickness in the normal population
There was less significant evidence for association with the measurements of other outer retinal layers in our dataset (Supplementary Table S5). This is the first study to analyse the relationship between AMD genetic polymorphisms and changes in outer retinal layer thickness in a large normal population
We focused our analysis on the outer retina as our hypothesis is that AMD related genes would affect photoreceptor and retinal pigment epithelium (RPE) thickness

Summary

Introduction

To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. A recent study examined the association of AMD susceptibility altering variants at CFH-CFHR5 and ARMS2/HTRA1 with macular retinal thickness in both normal individuals and those with A MD13. The UK Biobank is one of the largest prospective cohorts worldwide[16], with a wealth of medical, lifestyle and detailed genetic sequencing data, including extensive data on ophthalmic diseases This cohort provides the opportunity to investigate the impact of high-risk AMD genetic loci on changes in outer retinal layer thickness in clinically healthy participants from the UK Biobank population. This may provide mechanistic insight into how these genetic loci contribute to the development of AMD and identify novel biomarkers for clinical use

Methods

Results

Conclusion